[Colorectal tumor evolution in inflammatory bowel disease : Dynamics of genomic alterations and potential molecular...

Inflammatory bowel diseases (IBDs) increase the risk for colorectal cancer (CRC). In IBD, the evolution of potential tumor clones occurs long before neoplastic lesions become evident and these clones can be undetectable by endoscopy and histology at early stages. The spectrum of genomic alterations in IBD-associated colorectal carcinogenesis is distinct from the changes observed in the sporadic adenoma-carcinoma sequence. Predominant alterations include aneuploidies and mutations of TP53, which both occur early in IBD-related tumorigenesis. In some IBD patients, genomic alterations can already be detected in colonic mucosa without any histologic signs of dysplasia. Genomic analysis of multiregional samples from colectomy specimens of IBD patients revealed distinct tumor evolutionary patterns. This suggests an increased genomic instability in the chronically inflamed bowel that enables the emergence of multiple, phylogenetically unrelated neoplastic lesions within the colorectum of a single IBD patient. This article summarizes the genomic alterations underlying IBD-associated colorectal tumorigenesis and the evolutionary patterns from inflamed, not yet dysplastic epithelium to CRC. Furthermore, it is discussed how this knowledge can eventually be exploited for early detection of malignant progression of IBD and thus help to improve the clinical management and surveillance schedule of IBD patients.